Short-term effects of uranium on mucosal immunity in rat intestine.

  Dublineau I, Grison S, Baudelin C, Dudoignon N, Linard C, Souidi M, Marquette C and Aigueperse J. 33rd annual meeting of the european society for radiation biology, 25-28 aout 2004, Budapest, Hongrie.

  Objective. In case of chronic ingestion, the digestive tract is the first biological system exposed to daily intake of uranium in intestinal lumen. The increased uranium concentration in intestinal lumen and/or uranium accumulation in some intestinal cells may lead to functional modifications of intestine, notably in the intestinal barrier and the mucosal immunity. A recent study has demonstrated that contamination by heavy metal (e.g. lead) ingestion led to modifications of the gut immune system. However, no data are available in the literature on the effect of uranium ingestion on the immune intestinal functions. The objective of this study was thus to determine if mucosal immunity of intestine is modified in the first days following an acute ingestion of a sublethal dose of uranium.

Methods. The experiments are performed in Sprague-Dawley rats, which received an intragastric administration of depleted uranium (74 mg, pH = 3). The animals were euthanasied at one and three days after uranium administration. Intestinal segments were taking from distal ileum for i) standard histological analyses (HES staining) ii) immunohistochemical analyses of immune cells (macrophages, CD163 and intraepithelial lymphocytes, CD8) iii) tissue cytokine (IFNg) expression by RT-PCR and iiii) cytokine (IFNg, IL-2, Il-6, IL-12) and chemokine (MIP-2, MCP-1) production by ELISA.

Results. Pictures of macrophage staining in lamina propria and intraepithelial lymphocyte staining showed no modifications in localization and density of these two immune cell populations at day 1 and 3 post-contamination. Few changes in cytokine/chemokine production are observed at 1 and 3 days post-contamination. Only a 50% diminution of production of MCP-1 (p=0.05) and IL-12 (non significant) was observed at day 1. Tissue IFNg level was slightly increased at day 1 and 3. However, the IFNg expression measured 3 days after uranium contamination indicated a marked increased (x3.5) in mRNA level of this cytotoxic molecule.

Conclusion. These results indicated that uranium contamination at sublethal dose induced slight modifications of molecular and cellular actors implicated in intestinal immune response in the first days following uranium contamination. However, increased expression at day 3 of IFNg, a cytotoxic molecule notably for enterocytes, suggested that uranium may have deleterious effects at longer term (5 or 7 days) in intestinal functions, such as transport and immunity.